The UC San Diego Superfund Research Center (SRC) will investigate relationships linking obesity, nutrition, genetics, epigenetics and environmental toxicant exposure in the etiology and progression of liver disease, especially a non-alcoholic toxicant induced form of fatty liver disease called Toxicant-Associated Steatohepatitis (TASH). This focus is especially significant now given how cases of non-alcoholic fatty liver disease and hepatocellular carcinoma are dramatically increasing around the world, including in California and Mexico. Hispanic and Native Americans are especially vulnerable to this disease given their genetic susceptibility compounded by the harsh reality that many Hispanic and Native Americans live in stressed places with high rates of obesity, poverty, poor nutrition, health disparities and exposure to toxicants, all of which constitute cumulative impacts that increase the risk of getting cancer, including TASH. UC San Diego?s SRC is pursuing an innovative approach to understanding fatty liver disease and cancer. The Research Translation Core (RTC) will collaborate with all of the SRC project/core leaders to translate their scientific knowledge, data, models and technological innovations into forms useful for our target audiences?including the EPA, ATSDR, CDC, Nonprofits, Biotech, County health providers, city planning organizations, Tribal Environmental Agencies, the NIEHS and other SRCs. The RTC has access to urban and rural sites in California (San Diego and Imperial Valley), including the Halaco Superfund site, and Mexico (Tijuana) where place-based interventions are underway to reduce cumulative risks and health disparities impacting Hispanic and Native American communities. Our communication strategies, partnerships with government agencies, technology transfer and information dissemination to appropriate audiences will concentrate on toxicant induced liver disease from a perspective of prevention and intervention. We will identify and share new models of exposure (e.g., 3D printed liver tissue), methods of detection and diagnosis (e.g., Synthetically Evolved Receptors and Synthetically Evolved Biosensors), novel plant technologies (enhanced phytostabilization and bioremediation potential of plants and edible food safety) and new online cyberinfrastructure for data integration, visualization and mapping. The RTC will facilitate joint publications among project/core leaders and extend the reach of our science communication through social media, webinars, press releases, symposia, science cafes, geographic information systems and bioinformatics. This multidisciplinary team research will promote knowledge and understanding of how cumulative risks (e.g., obesity, poor nutrition, and exposure to toxicants) impact human health; thereby helping pave the way for better detection and diagnosis, prevention and interventions that can slow the rate of increase in toxicant induced liver disease.

Public Health Relevance

UC San Diego?s SRC is focusing on toxicant-associated steatohepatitis (TASH), a serious form of Non-Alcoholic Fatty Liver Disease (NAFLD). TASH and liver cirrhosis are on the rise in both children and adults; especially among Hispanic and Native Americans. Thus we expect that the science and technology emanating from our SRC will be relevant and useful to the U.S. EPA, ATSDR, state and local agencies, including health care providers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
2P42ES010337-16
Application #
9260649
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
2017-07-01
Budget End
2018-03-31
Support Year
16
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Tripathi, Anupriya; Debelius, Justine; Brenner, David A et al. (2018) The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 15:397-411
Chen, Shujuan; Tukey, Robert H (2018) Humanized UGT1 Mice, Regulation of UGT1A1, and the Role of the Intestinal Tract in Neonatal Hyperbilirubinemia and Breast Milk-Induced Jaundice. Drug Metab Dispos 46:1745-1755
Desai, Archita P; Mohan, Prashanthinie; Roubal, Anne M et al. (2018) Geographic Variability in Liver Disease-Related Mortality Rates in the United States. Am J Med 131:728-734
Ajmera, Veeral; Park, Charlie C; Caussy, Cyrielle et al. (2018) Magnetic Resonance Imaging Proton Density Fat Fraction Associates With Progression of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 155:307-310.e2
Ahmadian, Maryam; Liu, Sihao; Reilly, Shannon M et al. (2018) ERR? Preserves Brown Fat Innate Thermogenic Activity. Cell Rep 22:2849-2859
Tapper, Elliot B; Loomba, Rohit (2018) Nonalcoholic fatty liver disease, metabolic syndrome, and the fight that will define clinical practice for a generation of hepatologists. Hepatology 67:1657-1659
Tripathi, Anupriya; Debelius, Justine; Brenner, David A et al. (2018) Publisher Correction: The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 15:785
Zhang, Yuqin; Nasser, Victoria; Pisanty, Odelia et al. (2018) A transportome-scale amiRNA-based screen identifies redundant roles of Arabidopsis ABCB6 and ABCB20 in auxin transport. Nat Commun 9:4204
Tõldsepp, Kadri; Zhang, Jingbo; Takahashi, Yohei et al. (2018) Mitogen-activated protein kinases MPK4 and MPK12 are key components mediating CO2 -induced stomatal movements. Plant J 96:1018-1035
Li, Zixing; Takahashi, Yohei; Scavo, Alexander et al. (2018) Abscisic acid-induced degradation of Arabidopsis guanine nucleotide exchange factor requires calcium-dependent protein kinases. Proc Natl Acad Sci U S A 115:E4522-E4531

Showing the most recent 10 out of 404 publications